Jab1降解9-1-1引发DNA损伤修复障碍的机制研究

发布时间：2018-10-11 12:51

【摘要】：DNA损伤是细胞生命中的常见现象。各种各样的环境因素均可持续损害细胞内的遗传物质。这些因素包括来自太阳光的紫外线、电离辐射等外源因素，和来自体内物质代谢的氧化剂等内源因素。在长期的进化过程中，，针对各种代谢和外界来源的DNA损伤的因素，地球上的生物逐渐发展出一套完整的修复DNA损伤的机制，那就是高度保守的DNA损伤检控点和DNA修复。 DNA损伤检控点是指当DNA损伤时，延迟或阻滞细胞周期的生化过程。当DNA损伤时，该检控点途径的激活，能防止损伤的或复制不完全的遗传物质的传播，给细胞以足够的时间在细胞周期重新开始前，修复DNA损伤；或损伤过大时，启动凋亡或细胞衰老程序。DNA损伤检控点途径的缺陷，可引起突变的传播，导致其在体内的积累。而突变在体内的积累目前被认为可能是肿瘤发生最主要的原因。因此，DNA损伤时，DNA损伤检控点途径的激活，是维持遗传物质(染色体)的稳定性、抑制肿瘤发生所必需的。 Rad9-Rad1-Hus1(9-1-1)复合体是DNA损伤检控点途径中重要的感受器，DNA损伤时，该复合体在RFC-Rad17的帮助下，与损伤
[Abstract]:DNA damage is a common phenomenon in cell life. A variety of environmental factors can continue to damage the cell's genetic material. These factors include external factors such as ultraviolet radiation and ionizing radiation from the sun, and endogenous factors such as oxidizer from substance metabolism in the body. Over the course of a long evolutionary process, organisms on Earth have developed a complete mechanism for repairing DNA damage in response to various metabolic and external sources of DNA damage. That is the highly conserved DNA damage prosecution point and DNA repair. The DNA damage prosecution point is the biochemical process that delays or blocks the cell cycle when DNA is damaged. When DNA is damaged, the activation of the prosecution point pathway prevents the spread of damaged or incomplete genetic material, giving cells sufficient time to repair the DNA damage before the cell cycle restarts; or when the damage is excessive, To initiate the process of apoptosis or cell senescence. The defect of DNA damage control point pathway can cause the transmission of mutation and lead to its accumulation in vivo. The accumulation of mutations in the body is now thought to be the main cause of tumorigenesis. Therefore, during DNA damage, the activation of DNA damage checkpoint pathway is to maintain the stability of genetic material (chromosomes). Rad9-Rad1-Hus1 (9-1-1) complex is an important receptor in the pathway of DNA damage control point. When DNA is damaged, the complex is associated with injury with the help of RFC-Rad17.
【学位授予单位】：新疆医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R346

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